chr1-44757959-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006845.4(KIF2C):c.1120T>A(p.Tyr374Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Consequence
KIF2C
NM_006845.4 missense
NM_006845.4 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 7.70
Genes affected
KIF2C (HGNC:6393): (kinesin family member 2C) This gene encodes a kinesin-like protein that functions as a microtubule-dependent molecular motor. The encoded protein can depolymerize microtubules at the plus end, thereby promoting mitotic chromosome segregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.855
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF2C | NM_006845.4 | c.1120T>A | p.Tyr374Asn | missense_variant | 12/21 | ENST00000372224.9 | NP_006836.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF2C | ENST00000372224.9 | c.1120T>A | p.Tyr374Asn | missense_variant | 12/21 | 1 | NM_006845.4 | ENSP00000361298.4 | ||
KIF2C | ENST00000372217.5 | c.958T>A | p.Tyr320Asn | missense_variant | 11/20 | 1 | ENSP00000361291.1 | |||
KIF2C | ENST00000452259.5 | c.997T>A | p.Tyr333Asn | missense_variant | 11/11 | 5 | ENSP00000410346.1 | |||
KIF2C | ENST00000493027.5 | n.1082T>A | non_coding_transcript_exon_variant | 10/10 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74500
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2024 | The c.1120T>A (p.Y374N) alteration is located in exon 12 (coding exon 12) of the KIF2C gene. This alteration results from a T to A substitution at nucleotide position 1120, causing the tyrosine (Y) at amino acid position 374 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.99, 0.98
MutPred
0.67
.;Gain of disorder (P = 0.0133);.;
MVP
MPC
1.3
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at